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Memorial Butler lecture features studies in early Alzheimer’s diagnosis

May 29, 2013

Family, friends, colleagues, and the NIH scientific community celebrated the life of the NIA’s founding director May 8 at the Dr. Robert N. Butler Memorial Lecture. The lecture, part of the prestigious NIH Director’s Wednesday Afternoon Lecture Series, featured Dr. Ronald C. Petersen, director of the Mayo Clinic Study of Aging and the Mayo Alzheimer’s Research Center, as well as remarks about Dr. Butler by current NIA Director Dr. Richard Hodes. Lecture host NIH Director Dr. Francis Collins briefly discussed progress and opportunities in Alzheimer’s disease research as he introduced Dr. Petersen.

The NIA was founded in 1974 after a grass-roots campaign led by research advocates Florence Mahoney and Mary Lasker, joined by a cadre of congressional leaders, pushed for a national institute focused on diseases and conditions associated with advanced age. Dr. Butler, a passionate advocate for older people, was one of the first scientists to identify Alzheimer’s disease as a major challenge to healthy old age. Dr. Butler died July 4, 2010.

Dr. Petersen’s talk, “Neuroimaging and Biomarkers: How Early Can We Diagnose Alzheimer’s?” discussed the movement toward an earlier definition of Alzheimer’s disease, describing the recently revised diagnostic guidelines for Alzheimer’s disease that offer a new paradigm for the disease. The guidelines, issued by the NIA and the Alzheimer’s Association in 2011, define a spectrum of disease, starting with a presymptomatic phase detectable only by biomarkers and/or imaging, progressing to an intermediate phase of mild cognitive impairment (MCI) and, finally, to a phase marked by overt symptoms of dementia.

The guidelines are primarily being tested in research settings, as scientists look for ways to detect disease before symptoms appear. “Most things are falling into line,” Dr. Petersen said, “but there are a lot of questions that need to be answered.” The “million-dollar question” is whether the different types of neuroimaging and cerebrospinal fluid biomarkers researchers now use to detect the earliest brain changes of Alzheimer’s can predict who among cognitively normal people will develop Alzheimer’s and who will not, he said.

Scientists know that certain brain changes begin to occur about 15 years before memory loss and other symptoms of Alzheimer’s appear. The hope is to use neuroimaging and biomarkers to identify presymptomatic people who are destined to develop Alzheimer’s so they can get treatments that could prevent or stop the disease before it causes more brain damage.

To develop a predictive model, researchers are using scans that measure changes in brain structure, volume, and metabolism, as well as biomarkers that show changes in blood and cerebrospinal fluid, in different study populations, Dr. Petersen said. Some of Dr. Petersen’s work focuses on the Mayo Clinic Study of Aging, a population of about 3,000 older residents of Olmsted County, MN. The effort is a longitudinal study of normal aging and early cognitive impairment in a community setting.

The techniques used in these studies must be refined and validated in a general population before doctors can use them routinely in diagnosing Alzheimer’s or MCI, Dr. Petersen said. “So far, the data that are coming in are very consistent with what the theoretical model suggests,” he added. Researchers now know, for example, that individuals with MCI, beta-amyloid deposits, and neuronal injury in the brain are more likely to progress to dementia than those without those features.

Dr. Petersen noted that none of this research would have been possible without Dr. Butler, who was instrumental in establishing Alzheimer’s disease as an important area of research at NIA.